Changes in depression symptom profile with gender-affirming hormone use in transgender persons 87 We find significant differences between the changes in IDS-SR scores between the users of feminizing and masculinizing GAHT, and the opposing directions of the findings are is in line with depression in cisgender men and women. However, it must be noted that the absolute differences between the groups, with the TM group reporting an estimated 10% decline in depressive symptoms, which would translate into a median decrease of 1.5 points, and the TF group reporting an estimated increase of 16%, which would translate in a median increase of 1.8 points, resulting in an estimated 3.3 point difference in IDS-SR score changes after 12 months of GAHT. Although we had no predefined minimal clinically important difference, we believe that these changes might not directly translate into clinically significant effects. This discrepancy between the TM and TF groups is seen more specifically in the subscales of the clusters. The subscale for mood symptoms increases in the TF group by 24% after 12 months of GAHT but shows no significant changes in the TM group. The increase in mood symptoms in transgender women is in line with findings in the cisgender female population, where sex hormone interventions in reproductive-age participants have been associated with anhedonia and low mood (Frokjaer, 2020; Schiller et al., 2022). Secondly, the lethargy symptoms show no changes in the TF group, but a temporary decrease in the TM group after 3 months of GAHT. There are no studies on reported energy levels or lethargy symptoms in transgender testosterone users, but this finding is in line with a study in hypogonadal males, where 8 weeks of testosterone use resulted in decreased fatigue and increased vigor (O’Connor et al., 2002). The most important strengths of this current study are the prospective cohort design and the data-driven approach to studying depressive symptoms. The prospective, within-person design can more accurately give insight into changes in depressive symptoms after GAHT use, and the EFA analysis provided insight going further than the sum of all depressive symptoms, showing that especially mood and lethargy symptoms were prone to change after GAHT use. The identified subscales of the IDS-SR also enable further study into depression in transgender persons and GAHT use. However, there are several limitations that should be taken into account in the interpretation of our results. First, the study’s one-year follow-up period
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